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2015 ; 25
(7
): 785-800
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In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by
cell-in-cell structures
#MMPMID25916549
Ni C
; Chen Y
; Zeng M
; Pei R
; Du Y
; Tang L
; Wang M
; Hu Y
; Zhu H
; He M
; Wei X
; Wang S
; Ning X
; Wang M
; Wang J
; Ma L
; Chen X
; Sun Q
; Tang H
; Wang Y
; Wang X
Cell Res
2015[Jul]; 25
(7
): 785-800
PMID25916549
show ga
Epstein-Barr virus (EBV) can infect both susceptible B lymphocytes and
non-susceptible epithelial cells (ECs). Viral tropism analyses have revealed two
intriguing means of EBV infection, either by a receptor-mediated infection of B
cells or by a cell-to-cell contact-mediated infection of non-susceptible ECs.
Herein, we report a novel "in-cell infection" mechanism for EBV infection of
non-susceptible ECs through the formation of cell-in-cell structures. Epithelial
CNE-2 cells were invaded by EBV-infected Akata B cells to form cell-in-cell
structures in vitro. Such unique cellular structures could be readily observed in
the specimens of nasopharyngeal carcinoma. Importantly, the formation of
cell-in-cell structures led to the autonomous activation of EBV within Akata
cells and subsequent viral transmission to CNE-2 cells, as evidenced by the
expression of viral genes and the presence of virion particles in CNE-2 cells.
Significantly, EBV generated from in-cell infected ECs displayed altered tropism
with higher infection efficacy to both B cells and ECs. In addition to CNE-2
tumor cells, cell-in-cell structure formation could also mediate EBV infection of
NPEC1-Bmi1 cells, an immortalized nasopharyngeal epithelial cell line.
Furthermore, efficient infection by this mechanism involved the activation of the
PI3K/AKT signaling pathway. Thus, our study identified "in-cell infection" as a
novel mechanism for EBV infection. Given the diversity of virus-infected cells
and the prevalence of cell-in-cell structures during chronic infection, we
speculate that "in-cell infection" is likely a general mechanism for EBV and
other viruses to infect non-susceptible ECs.
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